Lysergic acid diethylamide, commonly called LSD, acid, or LSD-25, is a semisynthetic psychedelic drug. The short form LSD comes from the German "Lysergsäure-diethylamid". A typical single dose of LSD is between 100 and 500 micrograms, an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 20 micrograms[1] but most users may prefer to take larger doses.[2]

The effects of LSD can vary greatly depending on factors such as previous experiences, state of mind and environment (set and setting), as well as dose strength. Generally, LSD causes expansion and altered experience of senses, emotions, memories, time, and awareness for 8 to 14 hours, times vary depending on dosages and tolerance. In addition, LSD may produce visual effects such as moving geometric patterns, "trails" behind moving objects, and brilliant colors. LSD does not produce hallucinations in the strict sense, as it does not cause users to see things that aren't there, but instead illusions and vivid daydream-like fantasies, in which ordinary objects and experiences can take on entirely different appearances or meanings. At higher doses it can cause synesthesia. Some users cite the LSD experience as causing long-term or permanent changes in their personality and life perspective.

LSD is synthesized from lysergic acid derived from ergot, a grain fungus that typically grows on rye. LSD is sensitive to oxygen, ultraviolet light, and chlorine, especially in solution (though its potency may last years if the substance is stored away from light and moisture at low temperature). In pure form it is colorless, odorless (to humans; dogs can still be trained to smell LSD), and mildly bitter. LSD is typically delivered orally, usually on a substrate such as absorbent blotter paper, a sugar cube, or gelatin. In its liquid form, it can be administered by intramuscular or intravenous injection, or even in the form of eye-drops.

Introduced by Sandoz Laboratories as a drug with various psychiatric uses, LSD quickly became a therapeutic agent that appeared to show great promise. However, the extra-medical use of the drug in Western society in the middle years of the twentieth century led to a political firestorm that resulted in the banning of the substance for medical as well as recreational and spiritual uses. Despite this, it is still considered a promising drug in some intellectual circles, and organizations such as MAPS, Heffter Research Institute and the Albert Hofmann Foundation exist to fund, encourage and coordinate research into its medical uses.

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Perforated blotter paper impregnated with LSD, as illustrated above, is one popular form of dispensing the drug.

LSD was first synthesized in 1938 by Swiss chemist Dr. Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland, as part of a large research program searching for medically useful ergot alkaloid derivatives. Its psychedelic properties were unknown until 5 years later.

Until 1966, LSD and psilocybin were provided by Sandoz Laboratories free of charge to interested scientists under the trade name "Delysid".[3] The use of these compounds by psychiatrists to gain a better subjective understanding of the schizophrenic experience was an accepted practice. Many clinical trials were conducted on the potential use of LSD in psychedelic psychotherapy, generally with very positive results.

Cold War era intelligence services were keenly interested in the possibilities of using LSD for interrogation and mind control, and also for large-scale social engineering. The CIA conducted extensive research on LSD, which was mostly destroyed.[4] LSD was a central research area for Project MKULTRA, the code name for a CIA mind-control research program begun in the 1950s and continued until the late 1960s. Tests were also conducted by the U.S. Army Biomedical Laboratory (now known as the U.S. Army Medical Research Institute of Chemical Defense). Volunteers would take LSD and then perform a battery of tests to investigate the effects of the drug on soldiers. Based on remaining publicly available records, the projects seem to have concluded that LSD was of little practical use as a mind control drug and moved on to other drugs. Both the CIA and the Army experiments became highly controversial when they became public knowledge in the 1970s, as the test subjects were not normally informed of the nature of the experiments, or even that they were subjects in experiments at all. Several subjects developed severe mental illnesses and even committed suicide after the experiments. The controversy led to President Ford's creation of the Rockefeller Commission and new regulations on informed consent.

The British government also engaged in LSD testing; in 1953 and 1954, scientists working for MI6 dosed servicemen in an effort to find a "truth drug". The test subjects were not informed that they were being given LSD, and had in fact been told that they were participating in a medical project to find a cure for the common cold. One subject, aged 19 at the time, reported seeing "walls melting, cracks appearing in people's faces … eyes would run down cheeks, Salvador Dalí-type faces … a flower would turn into a slug". After keeping the trials secret for many years, MI6 agreed in 2006 to pay the former test subjects financial compensation. Like the CIA, MI6 decided that LSD was not a practical drug for brainwashing purposes.[5]

LSD first became popular recreationally among a small group of mental health professionals such as psychiatrists and psychologists during the 1950s, as well as by socially prominent and politically powerful individuals to whom the early LSD researchers were connected socially.

Several mental health professionals involved in LSD research, most notably Harvard psychology professors Drs. Timothy Leary and Richard Alpert, became convinced of LSD's potential as a tool for spiritual growth. In 1961, Dr. Timothy Leary received grant money from Harvard University to study the effects of LSD on test subjects. 3,500 doses were given to over 400 people. Of those tested, 90% said they would like to repeat the experience, 83% said they had "learned something or had insight," and 62% said it had changed their life for the better.

Their research became more esoteric and controversial, as Leary and Alpert alleged links between the LSD experience and the state of enlightenment sought after in many mystical traditions. They were dismissed from the traditional academic psychology community, and as such cut off from legal scientific acquisition of the drug. Drs. Leary and Alpert somehow acquired a quantity of LSD and relocated to a private mansion, where they continued their research. The experiments lost their scientific character as the pair evolved into countercultural spiritualgurus associated with the hippie movement, encouraging people to question authority and challenge the status quo, a concept summarized in Leary's catchphrase, "Turn on, tune in, drop out".

The drug was banned in the United States in 1967, with scientific therapeutic research as well as individual research also becoming prohibitively difficult. Many other countries, under pressure from the U.S., quickly followed suit. Since 1967, underground recreational and therapeutic LSD use has continued in many countries, supported by a black market and popular demand for the drug. Legal, academic research experiments on the effects and mechanisms of LSD are also conducted on occasion, but rarely involve human subjects. Despite its proscription, the hippie counterculture continued to promote the regular use of LSD, led by figures such as Leary and psychedelic rock bands such as The Grateful Dead.

According to Leigh Henderson and William Glass, two researchers associated with the NIDA who performed a 1994 review of the literature, LSD use is relatively uncommon when compared to the abuse of alcohol, cannabis, cocaine and prescription drugs. Over the previous fifteen years, long-term usage trends stayed fairly stable, with roughly 5% of the population using the drug and most users being in the 16 to 23 age range. Henderson and Glass found that LSD users typically partook of the substance on an infrequent, episodic basis, then "maturing out" after two to four years. Overall, LSD appeared to have comparatively few adverse health consequences, of which "bad trips" were the most commonly reported (and, the researchers found, one of the chief reasons youths stop using the drug).[6]

The dosage level that will produce a threshold hallucinogenic effect in humans is generally considered to be 20/30 μg, with the drug's effects becoming markedly more evident at higher dosages.[7][1] According to Glass and Henderson's review, black-market LSD is largely unadulterated though sometimes contaminated by manufacturing by-products. Typical doses in the 1960s ranged from 200 to 1000 µg, while street samples of the 1970s contained 30 to 300 µg. By the mid-1980s, the average had reduced to about 100 to 125 µg, lowering still further in the 1990s to the 20–80 µg range. (Lower doses, Glass and Henderson found, generally produce fewer bad experiences.)[6] Dosages by frequent users can be as high as 1,200 µg (1.2 mg), although such a high dosage may precipitate unpleasant physical and psychological reactions.

Estimates for the lethal dosage (LD50) of LSD range from 200 μg/kg to more than 1 mg/kg of human body mass, though most sources report that there are no known human cases of such an overdose. Other sources note one report of a suspected fatal overdose of LSD in which there were indications that ~1/3 of a gram (320 mg or 320,000 µg) had been injected intravenously, i.e., over 3,000 more typical oral doses of ~100 µg had been injected.[8]

LSD is not considered addictive, in that its users do not exhibit the medical community's commonly accepted definitions of addiction and physical dependence. Rapid tolerance build-up prevents regular use, and there is cross-tolerance shown between LSD, mescaline and psilocybin. This tolerance diminishes after a few days' abstention from use. As with any psychotropic substance there is a risk of psychological dependence; however, as with most psychedelics, this risk is relatively low [How to reference and link to summary or text].

LSD's secondary effects normally last from fifty-two to seventy-five hours,[2] though as Sandoz's prospectus for "Delysid" warned, "intermittent disturbances of affect may occasionally persist for several days."[3] Contrary to early reports and common belief, LSD effects do not last longer than significant levels of the drug in the blood. Aghajanian and Bing[9] found LSD had an elimination half-life of 175 minutes, while, more recently, Papac and Foltz[10]
reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 1.9 ng/mL at 3 hours post-dose. Notably, Aghajanian and Bing found that blood concentrations of LSD matched the time course of volunteers' difficulties with simple arithmetic problems.

Some reports indicate that administration of chlorpromazine (Thorazine) or similar typical antipsychotic tranquilizers will not end an LSD trip, it will rather become less intense or the side effects of the medication will immobilize and numb the patient.[11] While it also may not end an LSD trip, the best chemical treatment for a "bad trip" is an anxiolytic agent such as diazepam (Valium) or another benzodiazepine. Some have suggested that administration of niacin (nicotinic acid, vitamin B3) could be useful to end the LSD user's experience of a "bad trip".[12] The nicotinic acid in niacin as opposed to niacinamide, will produce a full body heat rash, due to widening of peripheral blood vessels. The effect is somewhat akin to a poison ivy rash. Although it is not clear to what extent the effects of LSD are reduced by this intervention, the physical effect of an itchy skin rash may itself tend to distract the user from feelings of anxiety. The rash itself is temporary and disappears within a few hours. It is not clear how effective this method would be for people having serious adverse psychological reactions.

Affinity of LSD for various receptors, averaged from data from the PDSP

LSD affects a large number of the G protein coupledreceptors, including all dopamine receptor subtypes, all adrenoreceptor subtypes as well as many others. LSD binds to most serotonin receptor subtypes except for 5-HT3 and 5-HT4. However, most of these receptors are affected at too low affinity to be activated by the brain concentration of approximate 10–20 nM.[13] Recreational doses of LSD can affect 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5 B and 5-HT6. The hallucinogenic effects of LSD are attributed to its strong partial agonist effects at 5-HT2A receptors as specific 5-HT2Aagonist drugs are hallucinogenic and largely 5-HT2A specific antagonists block the hallucinogenic activity of LSD.[13] Exactly how this produces the drug's effects is unknown, but it is thought that it works by increasing glutamate release and hence excitation in the cortex, specifically in layers IV and V.[14] In the later stages, LSD acts through DARPP-32 - related pathways that are likely the same for multiple drugs including cocaine, amphetamine, nicotine, caffeine, PCP, ethanol and morphine.[15] A particularly compelling look at the actions of LSD was performed by Barry Jacobs recording from electrodes implanted into cat raphe nuclei.[16] Behaviorally relevant doses of LSD result in a complete blockade of action potential activity in the dorsal raphe, effectively shutting off the principal endogenous source of serotonin to the telencephalon.

LSD was studied in the 1960s by Eric Kast as a painkiller for serious and chronic pain caused by cancer or other major trauma.[17] Even at low (sub-psychedelic) dosages, it was found to be at least as effective as traditional opiates while being much longer lasting (pain reduction lasting as long as a week after peak effects had subsided). Kast attributed this effect to a decrease in anxiety. This reported effect is being tested (though not using LSD) in an ongoing (as of 2006) study of the effects of the hallucinogen psilocybin on anxiety in terminal cancer patients.

Furthermore, LSD has been illicitly used as a treatment for cluster headaches, an uncommon but extremely painful disorder. Researcher Peter Goadsby describes the headaches as "worse than natural childbirth or even amputation without anesthetic."[18] Although the phenomenon has not been formally investigated, case reports indicate that LSD and psilocybin can reduce cluster pain and also interrupt the cluster-headache cycle, preventing future headaches from occurring. Currently existing treatments include various ergolines, among other chemicals, so LSD's efficacy may not be surprising. A dose-response study, testing the effectiveness of both LSD and psilocybin is, as of 2006, being planned at McLean Hospital. A 2006 study by McLean researchers interviewed 53 cluster-headache sufferers who treated themselves with either LSD or psilocybin, finding that a majority of the users of either drug reported beneficial effects.[19] Unlike attempts to use LSD or MDMA in psychotherapy, this research involves non-psychological effects and often sub-psychedelic dosages; therefore, it is plausible that a respected medical use of LSD will arise.[20]

LSD's psychological effects (colloquially called a "trip") vary greatly from person to person, from one trip to another, and even as time passes during a single trip. Widely different effects emerge based on what Leary called set and setting; the "set" being the general mindset of the user, and the "setting" being the physical and social environment in which the drug's effects are experienced.

An LSD trip can have long lasting or even permanent neutral, negative, and positive psychoemotional effects. LSD experiences can range from indescribably ecstatic to extraordinarily difficult; many difficult experiences (or "bad trips") result from a panicked user feeling they are going to die, are going to stay insane forever or that he or she has been permanently severed from reality and his or her ego. If the user is in a hostile or otherwise unsettling environment, or is not mentally prepared for the powerful distortions in perception and thought that the drug causes, effects are more likely to be unpleasant.

Conversely, a comfortable environment and a relaxed, balanced and open mindset will often result in a pleasant experience. A common advice is that the user should make sure to just go with the flow of the experience and not try to fight it.

Many users experience a dissolution between themselves and the "outside world": cognitive differences between subject ("I") and object ("me", "you", "it") break down or seem absurd.[21] This unitive quality may play a role in the spiritual and religious aspects of LSD.

Some experts hypothesize that drugs such as LSD may be useful in psychotherapy, especially when the patient is unable to "unblock" repressed subconscious material through other psychetherapeutic methods,[22] and also for treating alcoholism. One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"[23] presumably by forcing the user to face issues and problems in that individual's psyche. Many believe that, in contrast, other drugs (such as alcohol, heroin, and cocaine) are used to escape from reality. Studies in the 1950s that used LSD to treat alcoholism professed a 50% success rate,[24] higher than estimates near 10% for Alcoholics Anonymous.[25] Some LSD studies were criticized for methodological flaws, and different groups had inconsistent results. Mangini's 1998 paper reviews this history and concludes that the efficacy of LSD in treating alcoholism remains an open question.[26]

Many notable individuals have commented publicly on their experiences with LSD. Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to psychiatric treatment in the 1950s and 60s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

Generally beginning within thirty to ninety minutes after ingestion and continuing for the following six to twelve hours, the user may experience anything from subtle changes in perception to overwhelming cognitive shifts.

Changes in aural and visual perception are common, ranging from mild to profound.[21][27] These sensory changes include basic "high-level" distortions such as the appearance of moving geometric patterns, new textures on objects, blurred vision, image trailing, shape suggestibility and color variations. Inanimate objects are frequently described as "breathing". Users sometimes describe experiencing new, previously-unseen colors; sights and sounds may take on greater intensity or have more of an impact. Users commonly report that the inanimate world appears to animate in an unexplained way; that is, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.[28]

Higher doses often bring about shifts at a lower cognitive level, causing an intense and fundamental reinterpretation of sensory perception, symptomatic of synesthesia.

LSD is considered an entheogen because it often catalyzes intense spiritual experiences where users feel they have come into contact with a greater spiritual or cosmic order. It is common for users to achieve insights into the way the mind works and some users experience permanent or long-lasting changes in their life perspective because of what they have experienced. Some users consider LSD a religious sacrament, or a powerful tool for access to the divine. Many books have been written comparing the LSD trip to the state of enlightenment of eastern philosophy.

Such experiences under the influence of LSD have been observed and documented by researchers such as Timothy Leary and Stanislav Grof. For example, Walter Pahnke conducted the Good FridayMarsh Chapel Experiment under Leary's supervision, performing a double blind experiment on the administration of psilocybin to volunteers who were students in religious graduate programs, e.g., divinity or theology.[29] That study showed that hallucinogens could reliably be used to induce mystical religious states (at least in people with a spiritual predisposition).

Although LSD is generally considered nontoxic, it may temporarily impair the ability to make sensible judgments and understand common dangers, thus making the user susceptible to accidents and personal injury. For this reason it is usually suggested that a user have an experienced 'sitter' to watch over them.

There is also some indication that LSD may trigger a dissociative fugue state in individuals who are taking certain classes of antidepressants such as lithium salts and tricyclics. In such a state, the user has an impulse to wander, and may not be aware of his or her actions, which can lead to physical injury.[30]SSRIs are believed to interact more benignly, with a tendency to noticeably reduce LSD's subjective effects.[31] Similar and perhaps greater reductions have also been reported with MAOIs.[30]

As Albert Hofmann reports in LSD – My Problem Child, the early pharmacological testing Sandoz performed on the compound (before he ever discovered its psychoactive properties) indicated that LSD has a pronounced effect upon the mammalian uterus. Sandoz testing showed that LSD can stimulate uterine contractions with efficacy comparable to ergobasine, the active uterotonic component of the ergot fungus (Hofmann's work on ergot derivatives also produced a modified form of ergobasine which became a widely accepted medication used in obstetrics, under the trade name Methergine). LSD use by pregnant women is therefore contraindicated.[3]

Initial studies in the 1960s and 70s raised concerns that LSD might produce genetic damage or developmental abnormalities in fetuses. However, these initial reports were based on in vitro studies or were poorly controlled and have not been substantiated. In studies of chromosomal changes in human users and in monkeys, the balance of evidence suggests no significant increase in chromosomal damage. For example, studies were conducted with people who had been given LSD in a clinical setting.[32]White blood cells from these people were examined for visible chromosomal abnormalities. Overall, there appeared to be no lasting changes. Several studies have been conducted using illicit LSD users [citation needed] and provide a less clear picture. Interpretation of these data is generally complicated by factors such as the unknown chemical composition of "street" LSD and concurrent use of other psychoactive drugs. It seems possible that the small number of congenital abnormalities reported in users of street LSD is either coincidental or related to factors other than a toxic effect of pure LSD.

There is a reported possibility of "flashbacks", a psychological phenomenon in which an individual experiences an episode of some of the subjective effects of LSD (this may be a positive or negative experience) long after the drug has been consumed and worn off — sometimes weeks, months, or even years afterward.

Colloquial usage of the term "flashbacks" refers to any experience reminiscent of LSD effects; these are commonly occasional brief experiences. However, psychiatry recognizes a disorder in which LSD-like effects are persistent and cause clinically-significant impairment or distress. This chronic flashback syndrome is called Hallucinogen Persisting Perception Disorder (HPPD), a DSM-IV diagnosis. Several scientific journal articles have described the disorder.[33]

Several studies have tried to determine how likely a "normal" user (that is a user not suffering from known psychiatric conditions) of LSD is to experience flashbacks. The larger studies include Blumenfeld's in 1971[34] and Naditch and Fenwick's in 1977,[35] which arrived at figures of 20% and 28%, respectively. A recent review suggests that HPPD (according to the DSM-IV definition) caused by LSD appears to be rare and affects a distinctly vulnerable subpopulation of users.[36] Differences in the estimated prevalence of flashbacks may partly depend on the multiple meanings of the term and the fact that hallucinogen persisting perception disorder can only be diagnosed in a person who admits to their health care practitioner that they have used hallucinogens.

Debate continues over the nature and causes of chronic flashbacks. Some say HPPD is a manifestation of post-traumatic stress disorder, not related to the direct action of LSD on brain chemistry, and vary according to the susceptibility of the individual to the disorder. Many emotionally intense experiences can lead to flashbacks when a person is reminded acutely of the original experience. However, not all published case reports of chronic flashbacks appear to describe an anxious hyper-vigilant state reminiscent of post-traumatic stress disorder.

An alternative theory regarding flashbacks postulates that it is a form of perceptual learning. Although unusual perceptual experiences may be just as common among people with no history of having taken the drug, people who have taken LSD may be more likely to associate these otherwise normal psychological events with the experiences they remember having had while on LSD. Under this theory, HPPD would be a separate, more serious, and far less common psychological condition. "Mere" flashbacks, in comparison, may be experienced by a broad segment of the population, and only attributed to LSD by those who have tried the drug.

There are some cases of LSD inducing or triggering a psychosis in people who were apparently healthy prior to taking LSD. This issue was reviewed extensively in a 1984 publication by Rick Strassman.[37] In most cases, the psychosis-like reaction is of short duration, but in other cases it may be chronic. It is difficult to determine if LSD itself induces these reactions or if it merely triggers latent conditions that would have manifested themselves otherwise. The similarities of time course and outcomes between putatively LSD-precipitated and other psychoses suggests that the two types of syndromes are not different and that LSD may have been a nonspecific trigger. Several studies have tried to estimate the prevalence of LSD-induced prolonged psychosis arriving at numbers of around 4 in 1,000 individuals (0.8 in 1,000 volunteers and 1.8 in 1,000 psychotherapy patients in Cohen 1960;[38] 9 per 1,000 psychotherapy patients in Melleson 1971[39]). But these rates are far lower than the lifetime prevalence for psychotic conditions: schizophrenia, to pick just one type of psychosis, has a lifetime prevalence of about 1% in populations that are not exposed to LSD. In itself, this suggests no causative link between LSD and chronic psychotic disorders.

LSD is an example of an ergoline derivative. It is commonly produced from lysergic acid, which is made from ergotamine, a substance derived from the ergotfungus on rye, or from ergine (lysergic acid amide), a chemical found in morning glory and hawaiian baby woodrose seeds. It is theoretically possible to manufacture LSD from morning glory or hawaiian baby woodrose seed. LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD, has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from D-lysergic acid. However, LSD and iso-LSD, the two C-8 isomers, are rapidly interconverting in the presence of base. Non-psychoactive iso-LSD which has formed during the synthesis can be removed by chromatography and can be isomerized to LSD.

"LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule."[2] It is stable for indefinite amounts of time if stored, as a salt or in water, at low temperature and protected from air and light exposure. Two portions of its molecular structure are particularly sensitive, the carboxamide attachment at the 8-position and the double bond between the 8-position and the aromatic ring. The former is affected by high pH, and if perturbed will produce isolysergic acid diethylamide (iso-LSD), which is biologically inactive. If water or alcohol adds to the double bond (especially in the presence of light), LSD converts to "lumi-LSD", which is totally inactive in human beings, to the best of current knowledge. Furthermore, chlorine destroys LSD molecules on contact; even though chlorinated tap water typically contains only a slight amount of chlorine, because a typical LSD solution only contains a small amount of LSD, dissolving LSD in tap water is likely to completely eliminate the substance.[2]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[40] The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25 degrees C for up to 4 weeks. After 4 weeks of incubation, a 30% loss in LSD concentration at 37 degrees C and up to a 40% at 45 degrees C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. There was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA.

Only a small amount of ergotaminetartrate is required to produce LSD in large batches. For example, 25 kg of ergotamine tartrate can produce 5 or 6 kg of pure LSD crystal that, under ideal circumstances, could be processed into 100 million dosage units, assuming a typical "hit" of 125 μg. This is more than enough to meet what is believed to be the entire annual U.S. demand for the drug. LSD manufacturers only need to create a small quantity of the substance, and thus they enjoy an ease of transport and concealment not available to traffickers of other illegal drugs (such as cannabis and cocaine).[41]

Manufacturing LSD requires laboratory equipment and experience in the field of organic chemistry. It takes two or three days to produce 30 to 100 grams of pure compound. It is believed that LSD usually is not produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a synthesis step does not work as expected.[41]

LSD is produced in crystalline form and then mixed with excipients or diluted as a liquid for production in ingestible forms. Liquid solution is either distributed as-is in small vials or, more commonly, sprayed or soaked onto a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations forced a change to tablet form. Early pills or tabs were flattened on both ends and identified by color: "grey flat", "blue flat", and so forth. Next came "domes", which were rounded on one end, then "double domes" rounded on both ends, and finally small tablets known as "microdots". Later still, LSD began to be distributed in thin squares of gelatin ("window panes") and, most commonly, as blotter paper: sheets of paper impregnated with LSD and perforated into small squares of individual dosage units. The paper is then cut into small square pieces called "tabs" for distribution. Individual producers often print designs onto the paper serving to identify different makers, batches or strengths, and such "blotter art" often emphasizes psychedelic themes.

LSD is sold under a wide variety of street names including Acid, Trips, Alice Dee, 'Cid/Sid, Barrels, Blotter, Doses, "L", Liquid, Liquid A, Microdots, Mind detergent, Orange cubes, Orange micro, Owsley, Hits, Paper acid, Sacrament, Sandoz, Sugar, Sugar lumps, Sunshine, Tabs, Ticket, Twenty-five, Wedding bells, Windowpane, etc., as well as names that reflect the designs on the sheets of blotter paper.[42] On occasion, authorities have encountered the drug in other forms — including powder or crystal, and capsule. More than 200 types of LSD tablets have been encountered since 1969 and more than 350 paper designs have been observed since 1975. Designs range from simple five-point stars in black and white to exotic artwork in full four-color print.

LSD is easy to conceal and smuggle. A tiny vial can contain thousands of doses. Not much money is made from retail-level sales of LSD, so the drug is typically not associated with the violent organized criminal organizations involved in cocaine and opiate smuggling.

Prior to 1967, LSD was available legally in the United States as an experimental psychiatric drug. (LSD "apostle" Al Hubbard actively promoted the drug between the 1950s and the 1970s and introduced thousands of people to it.) The US Federal Government classified it as a Schedule I drug according to the Controlled Substances Act of 1970. As such, the Drug Enforcement Administration holds that LSD meets the following three criteria: it is deemed to have a high potential for abuse; it has no legitimate medical use in treatment; and there is a lack of accepted safety for its use under medical supervision. (LSD prohibition does not make an exception for religious use.) Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act. Ergotamine tartrate, a precursor to lysergic acid, is regulated under the Chemical Diversion and Trafficking Act.

LSD has been manufactured illegally since the 1960s. Historically, LSD was distributed not for profit, but because those who made and distributed it truly believed that the psychedelic experience could do good for humanity, that it expanded the mind and could bring understanding and love. A limited number of chemists, probably fewer than a dozen, are believed to have manufactured nearly all of the illicit LSD available in the United States. The best known of these is undoubtedly Augustus Owsley Stanley III, usually known simply as Owsley. The former chemistry student set up a private LSD lab in the mid-Sixties in San Francisco and supplied the LSD consumed at the famous Acid Test parties held by Ken Kesey and his Merry Pranksters, and other major events such as the Gathering of the tribes in San Francisco in January 1967. He also had close social connections to leading San Francisco bands the Grateful Dead, Jefferson Airplane and Big Brother and The Holding Company, regularly supplied them with his LSD and also worked as their live sound engineer and made many tapes of these groups in concert. Owsley's LSD activities — immortalized by Steely Dan in their song "Kid Charlemagne" — ended with his arrest at the end of 1967, but some other manufacturers probably operated continuously for 30 years or more. Announcing Owsley's first bust in 1966, The San Francisco Chronicle's headline "LSD Millionaire Arrested" inspired the rare Grateful Dead song "Alice D. Millionaire."

Pickard and Apperson ran an LSD lab in this former missile silo in Kansas.

American LSD usage declined in the 1970s and 1980s, then experienced a mild resurgence in popularity in the 1990s. Although there were many distribution channels during this decade, the U.S. DEA identified continued tours by the psychedelic rock band The Grateful Dead and the then-burgeoning rave scene as primary venues for LSD trafficking and consumption. American LSD usage fell sharply circa 2000. The decline is attributed to the arrest of two chemists, William Leonard Pickard, a Harvard-educated organic chemist, and Clyde Apperson. According to DEA reports, black market LSD availability dropped by 95% after the two were arrested in 2000. These arrests were a result of the largest LSD manufacturing raid in DEA history.[43]

Pickard was an alleged member of the Brotherhood of Eternal Love group that produced and sold LSD in California during the late 1960s and early 1970s. It is believed he had links to other "cooks" associated with this group — an original source of the drug back in the 1960's — and his arrest may have forced other operations to cease production, leading to the large decline in street availability.

The DEA claims these two individuals were responsible for the vast majority of LSD sold illegally in the United States and a significant amount of the LSD sold in Europe, and that they worked closely with organized traffickers. While this claim may have some bearing, the extent of Pickard's direct influence on the overall availability in the United States is not fully known. Some attest that "Pickard's Acid" was sold exclusively in Europe, and was not distributed through American music venues.

In November of 2003, Pickard was sentenced to life imprisonment without parole, and Apperson was sentenced to 30 years imprisonment without parole, after being convicted in Federal Court of running a large scale LSD manufacturing operation out of several clandestine laboratories, including a former missile silo near Wamego, Kansas.

LSD manufacturers and traffickers can be categorized into two groups: A few large scale producers, such as the aforementioned Pickard and Apperson, and an equally limited number of small, clandestine chemists, consisting of independent producers who, operating on a comparatively limited scale, can be found throughout the country. As a group, independent producers are of less concern to the Drug Enforcement Agency than the larger groups, as their product reaches only local markets.